DNA molecules are a natural substrate for fluidic manipulations given their enormous persistence length (approximately 500 angstroms), and intrinsic girth--a typical human chromosome contains a DNA molecule that spans about 1 inch, and forms a random coil with dimensions approaching approximately 10 mm. Given these physical properties, microfluidic devices will be easily engineered to elongate chains or direct their deposition onto surfaces for further analysis. The aim of this proposed research to fabricate, evaluate, and employ new devices based on recent insights drawn from sophisticated simulation studies of the dynamics of large DNA molecules within confined environments typified by micro and nanofluidic devices. New PDMS devices will feature a combination of nano approaches to molecular confinement combined with the simplicity of microscale devices to engender these new findings within a high-throughput, single molecule environment. Proven high-throughput single molecule analysis systems will be employed and extended to guide this development through the creation of statistically meaningful datasets with aims devoted to the development of new modalities for studying single molecule biochemistries. These new systems will be applied to transcriptional studies, and new approaches for the in vitro construction of very large single DNA molecule constructs. Together these new technologies bode well for the future of personalized medicine through the analysis of whole genome over large populations